Salts of the group III metal gallium have been known for some time to have antitumour activity. More recently, gallium has been shown to reduce serum calcium in patients with hypercalcemia of malignancy. Gallium exerts this latter effect by inhibiting the resorption of calcium from bone; it also increases bone strength so that gallium would also be useful for treating bone disorders associated with accelerated bone loss and decreased bone strength, (see e.g., U.S. Pat. No. 4,704,277 and U.S. Pat. No. 4,529,593).
In practice, gallium therapy for hypercalcemia has been difficult to provide. It has been reported that renal toxicity is dose-limiting when gallium is administered as an i.v. bolus. A seven day continuous i.v. infusion of gallium showed no renal toxicity for the treatment of cancer-associated hypercalcemia, and while this therapy is effective it is cumbersome. In order to make gallium therapy more conveniently administered for both cancer chemotherapy and the hypercalcemia of malignancy, and in order to provide wider application of gallium therapy to appropriate bone diseases, an oral dose form of gallium is highly desirable.
Drug absorption from the gastro-intestinal tract occurs at pH 4.5-7. In this pH range the gallium(III) aquo-ion is extensively hydrolysed to insoluble hydroxides and is very poorly absorbed. Daily oral doses of 400 mg GaCl.sub.3 in lung cancer patients yielded mean serum gallium concentrations of 371.+-.142 ug/mL. However, gallium in an appropriate co-ordination environment is stable to hydrolysis in aqueous environment, at pH which is relevant biologically.